Role of l -Carnitine in Apnea of Prematurity: A Randomized,Controlled Trial

Objective: Carnitine is thought to be a conditionally essential biologic cofactor for premature infants. A preliminary study suggested that carnitine could significantly reduce apnea of prematurity. The objective of this study was to evaluate critically the role of carnitine in idiopathic apnea of prematurity and to determine whether the use of carnitine would facilitate discontinuation of mechanical ventilatory support, shorten the duration of ventilatory support, and reduce the amount of time that such infants are exposed to both mechanical ventilation and oxygen. We also wanted to determine the effects of supplemental carnitine on weight gain, time to regain birth weight, time to achieve full enteral feedings, and length of hospital stay. Methods: A prospective, randomized, blinded trial was conducted on 44 preterm infants who were from the same neonatal intensive care unit and who were ≤32 weeks' gestational age with a postnatal age <48 hours and a birth weight <1500 g and required total parenteral nutrition (TPN). Infants were randomized to receive carnitine supplementation or placebo without crossover. Carnitine-supplemented infants received 30 mg/kg/d carnitine in their TPN until they were tolerating 120 mL/kg/d enteral feedings, and then they received 30 mg/kg/d oral carnitine. The placebo group received TPN without supplemental carnitine; when they tolerated 120 mL/kg/d enteral feedings, they received an oral placebo. The 2 groups continued on their respective supplemental carnitine or placebo until 34 weeks' adjusted age, at which time the study period was completed. Twelve-hour cardiorespiratorygrams to record heart rate, respiratory impedance, and oxygen saturation, and a nasal thermistor to detect expiratory airflow were performed every 4 days on 3 occasions and at 30 and 34 weeks' adjusted age. Plasma carnitine levels were measured at day 14. Results: There were no significant differences between the 2 groups in the occurrence of apnea as detected by cardiorespiratorygram or nursing observation. There were no significant differences between the groups in regard to total days on ventilator, days of nasal continuous positive airway pressure, time to regain birth weight, time to reach enteral feedings of 120 mL/kg/d, discharge weight, adjusted age at discharge, need for oxygen at 28 days' and 36 weeks' adjusted age, or length of stay. The plasma carnitine level was a median of 15.5 micromol/L (range: 7.6 to 30.5) for the placebo infants compared with a median of 195.3 micromol/L (range: 71.7 to 343.6) for the carnitine infants. Conclusions: In this blinded, randomized, placebo-controlled study, we found that infants who received supplemental carnitine did not demonstrate any reduction in apnea of prematurity, ventilator or nasal continuous positive airway pressure days, or the need for supplemental oxygen therapy. Although carnitine may be of significant nutritional benefit for very low birth weight infants, our study does not support its use to reduce apnea of prematurity or decrease dependence on mechanical ventilation.